This research proposal is based upon our observation that antibiotic killed extracellular bacteria activate proliferation of human lymphocytes in vitro. The aims of this research are to increase our knowledge of the interactions between pathogenic bacteria and human lymphocytes, and to explore if activated lymphocytes play a role in immunity to extracellular bacteria. The following studies are part of this proposal: 1) Studies on the nature of the in vitro lymphocyte response to killed bacteria. The basic method to be applied is the in vitro lymphocyte response (proliferation) measured by tritiated thymidine incorporation. Whole cell bacteria will be used as antigens (and/or mitogens). Variations of bacteria concentration, incubation time, cell populations (T- and B-lymphocytes and macrophages) and plasma fractions will be tested for this purpose. 2) Studies on the biologic significance of lymphocyte responsiveness to extracellular bacteria: Two functions have been selected for study: a) induction of in vitro biosynthesis of immunoglobulins, as determined by radioimmunoassay, and b) activation of phagocytic activity of macrophages and polymorphonuclear cells by products of lymphocytes stimulated by bacterial antigens. 3) Assessment of the qualitative and quantitative aspects of the responses in newborns (cord blood) and normal adults: After characterization in adults, some of the methods and variables described above will be applied comparatively to both normal adults and term newborns.